Fusogenic activity of pegylated ph-sensitive liposomes pdf

A phsensitive cationic lipid facilitates the delivery of liposomal sirna and gene silencing activity in vitro and in vivo yusuke sato a, hiroto hatakeyama a, b, yu sakurai a, mamoru hyodo a, hidetaka akita a, b, hideyoshi harashima a, b. We have reported that targeted, phsensitive sterically stabilized liposomes are able to increase the cytotoxicity of dxr in vitro against b lymphoma cells, but the rate of release of dxr in plasma was too rapid to permit the results to be extended to in vivo applications. Introduction immune mechanisms that control diseases include mainly the induction of neutralizing antibodies humoral immunity and generation of t cells cellmediated immunity. Research article efficiency of phsensitive fusogenic. The goal of this study is to bring biofunctionality to phsensitive pegylated liposomes in order to facilitate their potential use as a targeted drug delivery agent. We prepared phsensitive liposomes composed of the synthesized phsensitive amino lipid and studied the release behavior of albumin from the liposome under low ph and revealed the dynamics in. Potential of diallyl sulfide bearing phsensitive liposomes in chemoprevention against dmbainduced skin papilloma. Formulation, characterization and tissue distribution of a. Longcirculating pegylated phsensitive liposomes, despite having decreased ph sensitivity, still effectively deliver their contents into the cytoplasm. Efficiency of phsensitive fusogenic polymermodified. In this study, we displayed a phsensitive fusogenic gala peptide on the surface of a particle in order to confer the ability of endosomal escape to a zher2bnc. The cleavage of peg from carriers was achieved in response to the intracellular environment as well as the tumor microenvironment, which improvs cellular uptake and endosomal escape. A novel phsensitive liposome formulation containing oleyl alcohol.

Conventional liposomes were prepared using cholesterol and dipalmitoylsnglycero3phosphatidylethanolamine. Roux e, passirani c, scheffold s, benoit jp, leroux jc 2004 serumstable and longcirculating, pegylated phsensitive liposomes. Although phsensitive pegylated liposomes exhibits undesirable transfection efficiency compared to dccholdope liposomes, an increased accumulation in tumor tissues was observed in the administered complexes of dcchol dope 2. Finally, phsensitive liposomes using phsensitive lipids are described. Serumstable, longcirculating, phsensitive pegylated. Bleomycinloaded phsensitive polymerlipidincorporated. Pegbenzaldehydehydrazonecholesteryl hemisuccinate pegbhzchems containing hydrazone and ester bonds was synthesised and used to fabricate a dual ph.

Pharmacokinetic, biodistribution and therapeutic efficacy of 5fluorouracilloaded phsensitive pegylated liposomal nanoparticles in hct116 tumor bearing mouse ofonime udofot1, kevin affram1, taylor smith1, bulumko tshabe1, sunil krishnan2,mandip sachdeva1, and. The circulation time of liposomes in the bloodstream can be prolonged with the insertion of sterically stabilizing amphiphiles such as polyethylene glycol pegmodified phospholipids. Complexes containing cationic and anionic phsensitive. Serumstable, longcirculating pegylated phsensitive liposomes were also prepared using a combination of peg and a phsensitive, terminally alkylated copolymer of nisopropylacrylamide and. First generation phsensitive liposomes, based on the coneshaped lipid. Fusogenic activity of pegylated phsensitive liposomes vanic, z barnert, s suss, r schubert, r. These results suggest that the phsensitive fusogenic polymersucpg modified liposomes would serve effectively as an antigen delivery vehicle for inducing th1 and th2 immune responses. Pegylation can be used to extend the lifetime of liposomes in blood, but it had a negative influence on phsensitivity of complexes of dcchol dope liposomes and phsensitive pegylated liposomes. Surprisingly, the effect of the fusogenic peptide was dramatically reduced in the absence of r8. A phsensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of sirnacontaining nanoparticles in vitro and in vivo. Recent advances on thermosensitive and phsensitive. Formation strategies, mechanism of intracellular delivery and. Study of quercetinloaded liposomes as potential drug carriers. To fabricate an acidcleavable peg polymer for the development of pegcleavable phsensitive liposomes clppsl, and to investigate their ability for endosomal escape and long circulation.

Abstractthe phsensitive liposomes have been extensively used as an. An increase in peg molecular weight on the liposome surface significantly. Pdf to enhance the therapeutic benefit and to minimize associated toxicity, there. The phsensitive liposomes are a type of systems that release their contents. Pharmacokinetic, biodistribution and therapeutic efficacy. The addition of peg to the surface of liposomes reduced the res uptake and. An acetalbased pegylation reagent for phsensitive shielding of dna polyplexes. Observation with confocal laser scanning microscopy showed that these polymermodified liposomes were taken up efficiently by the cells, thereafter delivering their contents into the cytosol, probably through fusion. Effects of a novel phsensitive liposome with cleavable. Investigation of a fusogenic phsensitive liposomal system. Dual phsensitive liposomes with low phtriggered sheddable peg. Biodistribution studies and scintigraphic imaging were performed at. Steric stabilization of fusogenic liposomes by a lowph.

Liposomes composed of 10% of pod and 90% of a fusogenic lipid, dioleoyl. These phsensitive fusogenic liposomes encapsulating ovalbumin ova were applied to dc2. However, most of these new drugs fail to live up to their potential in the clinic. Liposomes from preformed vesicles ph induced vesiculation this method is used to transform mlvs to luvs using a change in the ph of the dispersion thus avoiding the use the sonication or high pressure application this process is electrostatic event and termed ph induced vesiculation. On the formulation of phsensitive liposomes with long. Repeated injections of pegylated liposomes elicit immune response and lead to production of antipeg igm, which enhances blood clearance of subsequently injected pegylated liposomes via antipeg. In drug delivery, nanosized pegylated phsensitive liposomes ppsl have been investigated as an effective drug carrier and solubiliser to confer improved tumour targeting. Normally, the bulk of liposomes together with their encapsulated material will enter the lysosomal pathway, where it will be exposed to a large panel of lytic. To assist the endosomal escape of inclusions, a helper lipid with phsensitive fusogenic ability 1,2dioleoylsnglycero3phos phoethanolamine. Fusogenic activity of pegylated phsensitive liposomes article in journal of liposome research 222.

The efficiency of the proposed system is quite high, even in the presence of serum, and shows improved targeting and selectivity. The goal of this study is to bring biofunctionality to. Observation with confocal laser scanning microscopy showed that these polymermodified liposomes were taken up efficiently by the cells, thereafter delivering their contents into the cytosol, probably through fusion with endosomal membranes. The modified phsensitive liposomes accumulate in tumor via the enhanced permeability and retention effect. Researchers have therefore used phsensitive liposomes that are sterically stabilized by polyethylene glycol peg molecules stealth liposomes on the liposome surface. Research paper targeting of sterically stabilised ph. Antibodymodified pegylated liposomes, immunoliposomes, are prepared by i.

The fusogenic behavior of these liposomes is due to the dope present in its lipid. Research paper targeting of sterically stabilised phsensitive liposomes to human tleukaemia cells cristina fonsecaa,b, joa. Alternative strategies to generate liposomes that are fusogenic under acidic conditions. The results indicated these complexes with phsensitive fusogenic liposomes exhibited higher transfection activity. Figure 10 shows that both phsensitive pegylated liposomes and the complexes of dccholdope liposomespdna and phsensitive pegylated liposomes had reduced ph sensitivity compared with their nonpegylated counterparts p sensitive fusogenic peptide. Pegderivatized lipid resulted in significantly reduced ph sensitivity 19. So phsensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via. Preparation of phsensitive liposomes composed of amino. Steric stabilization of fusogenic liposomes by a lowph sensitive. In this study, we prepared modified phsensitive liposomes with mpeghzchems, a cleavable peglipid derivative and control mpegchems. Full text formulation, characterization and tissue. Gene delivery to dendritic cells mediated by complexes of lipoplexes and phsensitive fusogenic polymermodified liposomes e yuba, c kojima, n sakaguchi, a harada, k koiwai, k kono journal of controlled release 1, 7783, 2008.

Antitumor activity of new liposomal prodrug of mitomycin c in multidrug resistant solid tumor. Preparation and characterization of phsensitive vesicles made of cholesteryl hemisuccinate. In the present study, we prepared polymermodified, plasma stable, phsensitive fusogenic mitoxantrone liposomes to increase efficacy and selectivity on cancer cell lines. Fusogenic liposomes effe ctively and directly deliver their encapsulated content s into the cytoplasm using a fusion mechanism of the sendai virus, wherea s conventio nal. The phsensitive lipid changes the headgroup charge according to ph.

A liposomebased antigen delivery system using phsensitive fusogenic polymers for cancer immunotherapy. To establish effective vaccine, moreover, we have developed ph sensitive liposomes, which generate fusion ability under weakly acidic conditions, by surface modification of liposomes with ph sensitive fusogenic polymer having carboxyl groups, such as succinylated poly glycidol sucpg and 3methylglutarylated poly glycidol mglupg. Due to their fusogenic and phsensitive properties, dopechems liposomes exploit the tumor extracellular ph phex. Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs. The use of phsensitive peptides or cationic lipids is considered an efficient strategy to enhance the cytoplasmic delivery of liposomal cargo by disrupting the endosomelysosome membrane following liposomal uptake by phagocytosis andor endocytosis.